首页|Effects of Regulating HSPA5 on Ferroptosis,Proliferation and Apoptosis of Cervical Cancer Cells in a Rat Model of Cervical Cancer
Effects of Regulating HSPA5 on Ferroptosis,Proliferation and Apoptosis of Cervical Cancer Cells in a Rat Model of Cervical Cancer
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Objective:To investigate the effects of regulating heat shock protein 70 protein 5 (HSPA5) on ferroptosis,proliferation and apoptosis of cervical cancer cells in a rat model of cervical cancer. Methods:A total of 48 SPF-grade healthy adult female Wistar rats were selected as the research objects. After adaptive feeding,U14 cells were intraperitoneally injected to construct a cervical cancer model. After successful modeling,the rats were randomly divided into four groups:the blank group was given normal saline by gavage for 7 d. The HM03+1-day group was given 10 mg/kg HM03 by gavage for 1 d followed by normal saline for 6 d,the HM03+3-day group was given 10 mg/kg HM03 by gavage for 3 d followed by normal saline for 4 d,and the HM03+7-day group was given 10 mg/kg HM03 by gavage for 7 d. Cervical lesion tissues of the rats were taken to prepare cell suspensions,which were then cultured to assess the expressions of HSPA5,glutathione peroxidase 4(GPX4),overoxidized peroxidase 3(SO2/3-PRDX3),and iron(Fe2+) in the cervical cancer cells,as well as the proliferation and apoptosis of the cervical cancer cells,were detected. Subsequently,6 cell suspensions from each group were treated with 10 μmol/L Ferrostatin-1(Fer-1) for 48 h,after which reactive oxygen species (ROS) and lactate dehydrogenase (LDH) expression were measured. Results:HSPA5 mRNA and protein expression in HM03-treated rat cervical cancer cells were significantly lower than those in the blank group (P<0.05),and with the extension of HM03 treatment time,HSPA5 mRNA and protein expression in rat cervical cancer cells were consequently lower (P<0.05). Relative expression of GPX4 protein in HM03-treated rat cervical cancer cells was significantly lower than that in the blank group (The relative expression of GPX4 protein in HM03-treated rat cervical cancer cells was significantly lower than that in the blank group (P<0.05),and the relative expression of SO2/3-PRDX3 protein and Fe2+expression level were significantly higher than that in the blank group,and with the extension of the treatment time of HM03,the relative expression of GPX4 protein in rat cervical cancer cells was reduced (P<0.05),and the relative expression of SO2/3-PRDX3 protein and Fe2+expression were increased. The proliferation of cervical cancer cells in HM03-treated rats was significantly reduced,the apoptosis was promoted,and the number of cells decreased,and with the extension of HM03 treatment,the proliferation of cervical cancer cells was reduced,and the rate of apoptosis was increased. After the rat cervical cancer cells were partially treated with Fer-1,the expression levels of both ROS and LDH were significantly reduced compared with those of the same group without Fer-1 treatment (P<0.05). Conclusion:Down-regulation of HSPA5 expression can reduce the proliferation ability of cervical cancer cells and promote apoptosis by activating ferroptosis in rat cervical cancer cells.
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